Romualdi D, Costantini B, Selvaggi L, Giuliani M, Cristello F, Macrì F, Bompiani A, Lanzone A, Guido M
Department of Obstetrics and Gynaecology, Università Cattolica del Sacro Cuore, L.go Agostino Gemelli, 8, 00168 Rome, Italy.
Hum Reprod. 2008 Sep;23(9):2127-33. doi: 10.1093/humrep/den230. Epub 2008 Jun 20.
Metformin was reported to improve the alterations of endothelial reactivity in normal-weight subjects with polycystic ovary syndrome (PCOS). The aim of the present study was to investigate the mechanisms of action of this drug on the vascular function of this population.
Thirteen normal-weight, normoinsulinemic and normolipemic PCOS women were studied before and after 6 months of metformin treatment (1000 mg/day). The endothelial function was assessed by evaluating the flow-mediated dilatation (FMD) of the brachial artery. We correlated this parameter with the endocrine-metabolic features of the patients.
Metformin significantly reduced testosterone (1.56 +/- 0.52 after 6 months versus 2.98 +/- 1.00 at baseline) and 17-hydroxyprogesterone (0.03 +/- 0.01 versus 0.06 +/- 0.02 nmol/ml) levels, without affecting gluco-insulinemic parameters. Concomitantly, the basal vessel diameter and the FMD significantly increased (4.12 +/- 0.68 versus 3.2 +/- 0.41 and 5.2 +/- 0.6 versus 3.76 +/- 0.5 mm, respectively), thus documenting an improved endothelial function.
Our data confirm the positive effects of metformin on the altered vascular reactivity, a precocious marker of cardiovascular risk, in normoinsulinemic PCOS subjects. This improvement seems to be mediated through hormonal changes, thus highlighting the detrimental role of hyperandrogenemia on the endothelial function, even beyond the metabolic factors. However, a direct effect of metformin on the endothelium should not be excluded.
据报道,二甲双胍可改善体重正常的多囊卵巢综合征(PCOS)患者的内皮反应性改变。本研究的目的是探讨该药物对这一人群血管功能的作用机制。
对13名体重正常、胰岛素水平正常且血脂正常的PCOS女性在接受二甲双胍治疗(1000毫克/天)6个月前后进行研究。通过评估肱动脉的血流介导的血管舒张(FMD)来评估内皮功能。我们将该参数与患者内分泌代谢特征进行关联。
二甲双胍显著降低了睾酮水平(6个月后为1.56±0.52,基线时为2.98±1.00)和17-羟孕酮水平(0.03±0.01与0.06±0.02纳摩尔/毫升),而不影响糖胰岛素参数。同时,基础血管直径和FMD显著增加(分别为4.12±0.68与3.2±0.41以及5.2±0.6与3.76±0.5毫米),从而证明内皮功能得到改善。
我们的数据证实了二甲双胍对胰岛素水平正常的PCOS患者血管反应性改变(心血管风险的早期标志物)具有积极作用。这种改善似乎是通过激素变化介导的,从而突出了高雄激素血症对内皮功能的有害作用,甚至超出了代谢因素的影响。然而,不应排除二甲双胍对内皮的直接作用。